Narrative: Hepatitis C virus is typically latent (i.e., silent) for decades; therefore, 80% to 85% of persons infected will not experience illness caused by the infection. Conversely, 15% to 20% of patients with untreated hepatitis will eventually develop liver failure or cancer.1 Standard treatment to prevent these developments includes interferon and ribavirin (Rebetol), a difficult-to-tolerate regimen that achieves SVR (i.e., the absence of virus in the blood) in approximately 50% of patients but is commonly associated with anemia and fatigue. The use of newer direct-acting antiviral agents may improve SVR rate and tolerability.2

The review summarized here addresses all major trials of second-generation direct-acting antiviral agents. To better understand the potentially unique benefits of this class, we focus on trials comparing any direct-acting antiviral-based regimen with interferon plus ribavirin. Despite 16 trials being identified, only five (all using simeprevir [Olysio]) were similar enough to be pooled. Simeprevir, when added to interferon and ribavirin, improved SVR without increasing adverse effects: 82% vs. 56% with the older regimen, a 26% absolute improvement (number needed to treat = 4).

Although pooled data for other agents such as daclatasvir (Daklinza, used in combination with sofosbuvir [Sovaldi]), ledipasvir (used in combination with sofosbuvir [Harvoni]), sofosbuvir, and paritaprevir (used in combination with ombitasvir and ritonavir [Norvir]) were unavailable (because of their indications to be used in combination with other